The isolation of .beta.-endorphins from mammalian brain and pituitary extracts has been described in the art. See for example Li and Chung, Proc. Natl. Acad. Sci. U.S.A. 73,1145 (1976) and U.S. Pat. No. 4,038,222. The availability of synthetic methods for preparing .beta.-endorphin has allowed studies into structure-activity relationships with analogs of .beta.-endorphin.
Initial modifications have been made in the amino terminal or enkephalin portion of the molecule, i.e., (1-5) .beta.-endorphin. Similar modifications made in enkephalin had produced enkephalin analogs with substantially enhanced analgesic activity over that of the parent compound. However, the .beta.-endorphin analogs, with the exception of [D-Ala.sub.2 ] - .beta.-endorphin, did not have the level of activity of the parent compound. See in this regard U.S. patent application Ser. No. 776,569, filed Mar. 11, 1977 and Yamashiro et al., Int. J. Pept. Prot. Res. 10,159 (1977).